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Best evidence yet that a single gene can affect IQ

By Andy Coghlan

16 April 2012

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Our genes account for a big chunk of the variability in intelligence, but no individual genes can take much credit for human smarts

(Image: Tetra Images/Getty Images)

A massive genetics study relying on MRI brain scans and DNA samples from over 20,000 people has revealed what is claimed as the biggest effect yet of a single gene on intelligence – although the effect is small.

There is little dispute that genetics accounts for a large amount of the variation in people’s intelligence, but studies have consistently failed to find any single genes that have a substantial impact. Instead, researchers typically find that hundreds of genes contribute.

Following a brain study on an unprecedented scale, an international collaboration has now managed to tease out a single gene that does have a measurable effect on intelligence. But the effect – although measurable – is small: the gene alters IQ by just 1.29 points. According to some researchers, that essentially proves that intelligence relies on the action of a multitude of genes after all.

“It seems like the biggest single-gene impact we know of that affects IQ,” says Paul Thompson of the University of California, Los Angeles, who led the collaboration of 207 researchers. “But it’s not a massive effect on IQ overall,” he says.

Two teaspoons

The variant is in a gene called HMGA2, which has previously been linked with people’s height. At the site of the relevant mutation, the IQ difference depends on a change of a single DNA “letter” from C, standing for cytosine, to T, standing for thymine.

“C is the good one,” says Thompson. As well as raising IQ by 1.29, it increases the overall volume of the brain – but only by 0.58 per cent of average brain size, adding around 9 cubic centimetres of tissue. “It’s a loss or gain of about 2 teaspoons,” says Thompson.

The brain-size-altering effect of the gene is what led the researchers to study the impact on IQ. In their study, involving 21,151 adult subjects, they took DNA samples but also scanned each volunteer’s brain, specifically looking for size differences either in the brain overall or in specific parts of it, such as the hippocampus, thought to be the seat of memory and learning.

C-ing double

After the researchers had established that HMGA2 affected overall brain size, they looked in more detail at a subset of 1642 volunteers from a twin study in Brisbane, Australia, who had all taken standard IQ tests. From that analysis, they were then able to measure the effect of the C on IQ. When people inherit C-variants from both parents they enjoy double the effect: a rise in IQ of about 2.6.

“It’s important they’ve found this gene, but it took a sample of 20,000 people to find it, precisely because the effect is so small,” says Robert Plomin at the Institute of Psychiatry in London, and lead author of a groundbreaking study in 2007 which failed to find any single genes of disproportionate importance in intelligence. “If it’s this hard to find an effect of just 1 per cent, what you’re really showing is that the ‘cup’ is 99-per-cent empty,” he says.

Steven Pinker, an author and professor of neuropsychology at Harvard University, agrees. “It’s an important finding, assuming it holds up,” he says. Pinker says that the findings are a first step in demonstrating that intelligence relies on large numbers of genes, each with a tiny effect, rather than on single genes that have moderate or large effects, but which are so rare that none has yet been identified.

Brain ager

The other key finding by Thompson’s team was that a variant of a gene called TESC affects the size of the hippocampus, altering its size by 1.2 per cent above or below the average.

Thompson says that in adulthood, the hippocampus shrinks by about 0.5 per cent per year, so having the “wrong” gene variant can equate to more than two years of ageing, and having two copies of it is equivalent to five years of ageing – all of which could hasten the arrival of dementia or other diseases related to hippocampus shrinkage, including Alzheimer’s disease and depression.

Thompson says, however, that the effects of TESC can be countered by regular exercise, which increases the size of the hippocampus by a corresponding amount and improves memory (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1015950108).

Journal reference: Nature Genetics, DOI: 10.1038/ng.2250

When this article was first posted, the gene affecting hippocampal size was incorrectly named TERT

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